Semisynthetic Organism: The Pursuit

Scientist and genomic researchers are always in the pursuit of improving the quality of life by creating artificial life based on different molecular components. Scientists have come across never heard of challenges trying to scale this uncharted terrain and have made little success in the recent past.

In 2014, scientists were successful to come up with semisynthetic organism with an unnatural base pair of six unnatural base pair extended from the usual four letter genetic alphabet. But the success did not last long as the organism grew poorly losing unnatural base pairs over time when outside lab environment. Researchers have recently a healthier version that grows well retaining the unnatural base pairs.

Team at Romesberg worked with Escherichia coli. They added a transporter in the E.Coli that moves unnatural triphosphates that are broken down to be incorporated into the DNA in the cells. The research team truncated the transporter making it less toxic and traded different base for one of the bases in the unnatural base pair. All this improved the retention of the unnatural base pair. But when the organism grew in certain culture conditions in some sequence contexts the semisynthetic organism lost the unnatural base pair.

CRISPR was used to immunize the failing semisynthetic organism and to retain its unnatural base pair. Plasmids containing both the unnatural base pair and guide sequences were introduced that facilitate the plasmid’s cleavage by endonuclease Cas9. Minimal loss in all culture conditions and across the majority of sequence contexts was achieved using the CRISPR-based strategy

With this major breakthrough the way forward is to be able to control gene expression containing these unnatural bases and produce artificial proteins with unnatural amino acids. With this major genetic questions in origin of life could be answered.